Flow-accelerated platelet biogenesis is due to an elasto-hydrodynamic instability.

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Blood platelets are essential for hemostasis and are produced by bone marrow megakaryocytes.
• The precise biophysical mechanism of platelet formation, particularly fragmentation from megakaryocyte extensions, remains incompletely understood.
• External blood flow is known to influence platelet biogenesis, but the underlying physical principles are not fully elucidated.

Purpose of the Study:

• To elucidate the biophysical mechanism driving the fragmentation of megakaryocyte extensions into platelets.
• To investigate the role of cellular active processes and external flow dynamics in platelet formation.
• To understand how fragmentation dynamics influence final platelet size and biogenesis rates.

Main Methods:

• Utilized lattice-Boltzmann and immersed boundary simulations to model megakaryocyte fragmentation.
• Developed a three-dimensional computational model incorporating active cortical processes like actomyosin contractility and microtubule sliding.
• Simulated the effects of different external flow conditions (homogeneous and shear flow) on the fragmentation process.

Main Results:

• Identified a biological Rayleigh-Plateau instability, driven by actomyosin contractility, as the key mechanism for platelet fragmentation.
• Demonstrated that the wavelength of the instability dictates the size of the resulting platelets.
• Showed that external flow significantly accelerates platelet biogenesis, with homogeneous flow yielding the strongest acceleration.
• Observed that shear flow can induce fusion events between developing platelet swellings, leading to larger structures (preplatelets).

Conclusions:

• Platelet fragmentation is primarily governed by physical principles, specifically an elasto-hydrodynamic instability.
• Actomyosin contractility is essential for initiating the fragmentation instability.
• External flow dynamics play a crucial role in accelerating platelet production and can influence platelet size through fusion events.
• The findings provide a physical explanation for flow-accelerated platelet biogenesis and size regulation.